tbuckley/cabot-search huggingface dataset:
Prostate-specific Membrane Antigen Reporting and Data System Version 2.0
Authors: Rudolf A. Werner, Philipp E. Hartrampf, Wolfgang P. Fendler, Sebastian E. Serfling, Thorsten Derlin, Takahiro Higuchi, Kenneth J. Pienta, Andrei Gafita, Thomas A. Hope, Martin G. Pomper, Matthias Eiber, Michael A. Gorin, Steven P. Rowe
Journal: European Urology (2023)

Prostate-specific Membrane Antigen Reporting and Data System (PSMA-RADS) was introduced for standardized reporting, and PSMA-RADS version 1.0 allows classification of lesions based on their likelihood of representing a site of prostate cancer on PSMA-targeted positron emission tomography (PET). In recent years, this system has extensively been investigated. Increasing evidence has accumulated that the different categories reflect their actual meanings, such as true positivity in PSMA-RADS 4 and 5 lesions. Interobserver agreement studies demonstrated high concordance among a broad spectrum of 68Ga- or 18F-labeled, PSMA-directed radiotracers, even for less experienced readers. Moreover, this system has also been applied to challenging clinical scenarios and to assist in clinical decision-making, for example, to avoid overtreatment in oligometastatic disease. Nonetheless, with an increasing use of PSMA-RADS 1.0, this framework has shown not only benefits, but also limitations, for example, for follow-up assessment of locally treated lesions. Thus, we aimed to update the PSMA-RADS framework to include a refined set of categories in order to optimize lesion-level characterization and best assist in clinical decision-making (PSMA-RADS version 2.0).
A commentary on ‘The experience of neoadjuvant chemotherapy versus upfront surgery in resectable pancreatic cancer: a cross sectional study’
Authors: Yuan Chen, Chengcheng Wang, Yupei Zhao
Journal: International Journal of Surgery (2023)

Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100023, PR China Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding author. Address: Yupei Zhao, Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100023, PR China. Email: [email protected] This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc/4.0/
Relative efficacy and safety of several regional analgesic techniques following thoracic surgery: a network meta-analysis of randomized controlled trials
Authors: Jie Li, Qingchao Sun, Liang Zong, Desheng Li, Xiaoliang Jin, Liwei Zhang
Journal: International Journal of Surgery (2023)

Background: This network meta-analysis was performed to assess the relative efficacy and safety of various regional analgesic techniques used in thoracic surgery. Materialsand methods: Randomized controlled trials evaluating different regional analgesic methods were retrieved from databases, including PubMed, Embase, Web of Science, and the Cochrane Library, from inception to March 2021. The surface under the cumulative ranking curve) was estimated to rank the therapies based on the Bayesian theorem. Moreover, sensitivity and subgroup analyses were performed on the primary outcomes to obtain more reliable conclusions. Results: Fifty-four trials (3360 patients) containing six different methods were included. Thoracic paravertebral block and erector spinae plane block (ESPB) were ranked the highest in reducing postoperative pain. As for total adverse reactions and postoperative nausea and vomiting, postoperative complications, and duration of hospitalization, ESPB was found to be superior to other methods. It should be noted that there were few differences between various methods for all outcomes. Conclusions: Available evidence suggests that ESPB might be the most effective and safest method for relieving pain after thoracic surgery, shortening the length of hospital stay and reducing the incidence of postoperative complications.
Polyglycerol‐Based Biomedical Matrix for Immunomagnetic Circulating Tumor Cell Isolation and Their Expansion into Tumor Spheroids for Drug Screening
Authors: Peng Tang, Boonya Thongrom, Smriti Arora, Rainer Haag
Journal: Advanced Healthcare Materials (2023)

Circulating tumor cells (CTCs) are established as distinct cancer biomarkers for diagnosis, as preclinical models, and therapeutic targets. Their use as preclinical models is limited owing to low purity after isolation and the lack of effective techniques to create 3D cultures that accurately mimic in vivo conditions. Herein, a two-component system for detecting, isolating, and expanding CTCs to generate multicellular tumor spheroids that mimic the physiology and microenvironment of the diseased organ is proposed. First, an antifouling biointerface on magnetic beads is fabricated by adding a bioinert polymer layer and conjugation of biospecific ligands to isolate cancer cells, dramatically enhancing the selectivity and purity of the isolated cancer cells. Next, the isolated cells are encapsulated into self-degradable hydrogels synthesized using a thiol-click approach. The hydrogels are mechanochemically tuned to enable tumor spheroid growth to a size greater than 300 µm and to further release the grown spheroids while retaining their tumor-like characteristics. In addition, drug treatment highlights the need for 3D culture environments rather than conventional 2D culture. The designed biomedical matrix shows potential as a universal method to ensure mimicry of in vivo tumor characteristics in individual patients and to improve the predictability of preclinical screening of personalized therapeutics.
Safety and immunogenicity of a novel multivalent OspA-based vaccine candidate against Lyme borreliosis: a randomised, phase 1 study in healthy adults
Authors: Nicole Bézay, Romana Hochreiter, Vera Kadlecek, Nina Wressnigg, Julian Larcher-Senn, Anton Klingler, Katrin Dubischar, Susanne Eder-Lingelbach, Isabel Leroux-Roels, Geert Leroux-Roels, Wolfgang Bender
Journal: The Lancet Infectious Diseases (2023)
A Versatile G‐Quadruplex (G4)‐Coated Upconverted Metal‐Organic Framework for Hypoxic Tumor Therapy
Authors: Xuanxiang Mao, Xiaobo Zhang, Zhicong Chao, Dehui Qiu, Shijiong Wei, Rengan Luo, Desheng Chen, Yue Zhang, Yun Chen, Yuanjiao Yang, David Monchaud, Huangxian Ju, Jean‐Louis Mergny, Jianping Lei, Jun Zhou
Journal: Advanced Healthcare Materials (2023)

Given the complexity of the tumor microenvironment, multiple strategies are being explored to tackle hypoxic tumors. The most efficient strategies combine several therapeutic modalities and typically requires the development of multifunctional nanocomposites through sophisticated synthetic procedures. Herein, the G-quadruplex (G4)-forming sequence AS1411-A (d[(G2 T)4 TG(TG2 )4 A]) is used for both its anti-tumor and biocatalytic properties when combined with hemin, increasing the production of O2 ca. two-fold as compared to the parent AS1411 sequence. The AS1411-A/hemin complex (GH) is grafted on the surface and pores of a core-shell upconverted metal-organic framework (UMOF) to generate a UMGH nanoplatform. Compared with UMOF, UMGH exhibits enhanced colloidal stability, increased tumor cell targeting and improved O2 production (8.5-fold) in situ. When irradiated by near-infrared (NIR) light, the UMGH antitumor properties are bolstered by photodynamic therapy (PDT), thanks to its ability to convert O2 into singlet oxygen (1 O2 ). Combined with the antiproliferative activity of AS1411-A, this novel approach lays the foundation for a new type of G4-based nanomedicine.
Harnessing 3D in vitro systems to model immune responses to solid tumours: a step towards improving and creating personalized immunotherapies
Authors: Zhenzhen Zhou, Yuan Pang, Jingyuan Ji, Jianyu He, Tiankun Liu, Liliang Ouyang, Wen Zhang, Xue-Li Zhang, Zhi-Gang Zhang, Kaitai Zhang, Wei Sun
Journal: Nature reviews. Immunology (2023)
Molecular correlates of vaccine-induced protection against typhoid fever
Authors: Henderson Zhu, Irina Chelysheva, Deborah L. Cross, Luke Blackwell, Celina Jin, Malick M. Gibani, Elizabeth Jones, Jennifer Hill, Johannes Trück, Dominic F. Kelly, Christoph J. Blohmke, Andrew J. Pollard, Daniel O’Connor
Journal: Journal of Clinical Investigation (2023)

BACKGROUNDTyphoid fever is caused by the Gram-negative bacterium Salmonella enterica serovar Typhi and poses a substantial public health burden worldwide. Vaccines have been developed based on the surface Vi-capsular polysaccharide of S. Typhi; these include a plain-polysaccharide-based vaccine, ViPS, and a glycoconjugate vaccine, ViTT. To understand immune responses to these vaccines and their vaccine-induced immunological protection, molecular signatures were analyzed using bioinformatic approaches.METHODSBulk RNA-Seq data were generated from blood samples obtained from adult human volunteers enrolled in a vaccine trial, who were then challenged with S. Typhi in a controlled human infection model (CHIM). These data were used to conduct differential gene expression analyses, gene set and modular analyses, B cell repertoire analyses, and time-course analyses at various post-vaccination and post-challenge time points between participants receiving ViTT, ViPS, or a control meningococcal vaccine.RESULTSTranscriptomic responses revealed strong differential molecular signatures between the 2 typhoid vaccines, mostly driven by the upregulation in humoral immune signatures, including selective usage of immunoglobulin heavy chain variable region (IGHV) genes and more polarized clonal expansions. We describe several molecular correlates of protection against S. Typhi infection, including clusters of B cell receptor (BCR) clonotypes associated with protection, with known binders of Vi-polysaccharide among these.CONCLUSIONThe study reports a series of contemporary analyses that reveal the transcriptomic signatures after vaccination and infectious challenge, while identifying molecular correlates of protection that may inform future vaccine design and assessment.TRIAL REGISTRATIONClinicalTrials.gov NCT02324751.
Invisible no more: unpaid care giving in the shadow of covid-19
Authors: Miles Sibley, Laila Hallam, Sue Robins
Journal: BMJ (2023)

Invisible no more: unpaid care giving in the shadow of covid-19Miles Sibley and colleagues argue that families must be recognised and valued as partners in patient care C ovid-19 brought radical shifts in healthcare policies and practice, including the abandonment of families as partners in care.This happened in multiple countries, including Australia, Canada, and the UK, which are all high income countries with mixed public and private healthcare as well as being our home countries.In response to covid-19, England, introduced blanket bans on visiting hospitals and care homes-a practice that was subsequently condemned in parliament. 1 In maternity services, the presence of birth partners was restricted, leading to a deterioration in women's experiences of care. 2 Strict visitor restrictions in Canada did not differentiate between visitors and essential care partners, and caregivers were prevented from providing supportive care to their family members in health and care facilities. 3 Australia saw immediate visitor bans and, later, exception based visitor permissions in hospitals and residential care.Consumer partners who engage in health organisational design and governance were also excluded from decision making in response to covid-19.This resulted in pandemic decisions being made without consumer stakeholders to advocate for patients and families. 4atients define their own "family" and determine how they will participate in care and decision making. 5As such, the term can include one or more people and can include family members, friends, carers, informal carers, caregivers, and other partners in care who provide unpaid care and support.The swift exclusion of families during the pandemic exposed systems that do not recognise families as fundamental contributors to patient care and outcomes and to safe and effective health systems.
Assessing resilience of a health system is difficult but necessary to prepare for the next crisis
Authors: Anna Sagan, Steve Thomas, Erin Webb, Martin McKee
Journal: BMJ (2023)

Assessing resilience of a health system is difficult but necessary to prepare for the next crisis Health systems responses to covid-19 can help to identify factors within and outside of the health system that affect its resilience to shocks, suggest Anna Sagan and colleagues Key messages• Health systems are often unprepared for shocks such as covid-19, but assessing resilience can help them prepare• Health system resilience to a shock is difficult to measure comprehensively• It can, however, be assessed by look- ing at what absorptive, adaptive, and transformative measures health systems adopted in response to a shock• Responses to covid-19 show how health system strengthening and factors outside the health system affect resilience on
MTMR3 risk alleles enhance Toll Like Receptor 9-induced IgA immunity in IgA nephropathy
Authors: Yan-na Wang, Ting Gan, Shu Qu, Lin-lin Xu, Yong Hu, Li-jun Liu, Su-fang Shi, Ji-cheng Lv, Lam C. Tsoi, Matthew T. Patrick, Kevin He, Celine C. Berthier, Hu-ji Xu, Xu-jie Zhou, Hong Zhang
Journal: Kidney International (2023)
Long-term outcomes to neoadjuvant pembrolizumab based on pathological response for patients with resectable stage III/IV cutaneous melanoma
Authors: C.E. Sharon, G.N. Tortorello, K.L. Ma, A.C. Huang, X. Xu, L.R. Giles, S. McGettigan, K. Kreider, L.M. Schuchter, A.J. Mathew, R.K. Amaravadi, P.A. Gimotty, J.T. Miura, G.C. Karakousis, T.C. Mitchell
Journal: Annals of Oncology (2023)
Genome editing in the mouse brain with minimally immunogenic Cas9 RNPs
Authors: Elizabeth C. Stahl, Jennifer K. Sabo, Min Hyung Kang, Ryan Allen, Elizabeth Applegate, Shin Eui Kim, Yoonjin Kwon, Anmol Seth, Nicholas Lemus, Viviana Salinas-Rios, Katarzyna M. Soczek, Marena Trinidad, Linda T. Vo, Chris Jeans, Anna Wozniak, Timothy Morris, Athen Kimberlin, Thomas Foti, David F. Savage, Jennifer A. Doudna
Journal: Molecular Therapy (2023)

Transient delivery of CRISPR-Cas9 ribonucleoproteins (RNPs) into the central nervous system (CNS) for therapeutic genome editing could avoid limitations of viral vector-based delivery including cargo capacity, immunogenicity, and cost. Here, we tested the ability of cell-penetrant Cas9 RNPs to edit the mouse striatum when introduced using a convection-enhanced delivery system. These transient Cas9 RNPs showed comparable editing of neurons and reduced adaptive immune responses relative to one formulation of Cas9 delivered using AAV serotype 9. The production of ultra-low endotoxin Cas9 protein manufactured at scale further improved innate immunity. We conclude that injection-based delivery of minimally immunogenic CRISPR genome editing RNPs into the CNS provides a valuable alternative to virus-mediated genome editing.
Correction:<i>Efficacy and safety of bimekizumab in axial spondyloarthritis: results of two parallel phase 3 randomised controlled trials</i>
Journal: Annals of the Rheumatic Diseases (2023)

Although the results were presented correctly, the summary in the discussion needs to be corrected:'Most fungal infections with bimekizumab were mild to moderate, and none were systemic or led to treatment discontinuation.'Correct sentence: 'Most cases of fungal infections with bimekizumab were mild to moderate, with only 2 leading to discontinuation, and no systemic fungal infections were reported.'
Neural Decoding for Intracortical Brain–Computer Interfaces
Authors: Yuanrui Dong, Shirong Wang, Qiang Huang, Rune W. Berg, Guanghui Li, Jiping He
Journal: Cyborg and Bionic Systems (2023)

Brain–computer interfaces have revolutionized the field of neuroscience by providing a solution for paralyzed patients to control external devices and improve the quality of daily life. To accurately and stably control effectors, it is important for decoders to recognize an individual's motor intention from neural activity either by noninvasive or intracortical neural recording. Intracortical recording is an invasive way of measuring neural electrical activity with high temporal and spatial resolution. Herein, we review recent developments in neural signal decoding methods for intracortical brain–computer interfaces. These methods have achieved good performance in analyzing neural activity and controlling robots and prostheses in nonhuman primates and humans. For more complex paradigms in motor rehabilitation or other clinical applications, there remains more space for further improvements of decoders.
Overexpression of human alpha-Synuclein leads to dysregulated microbiome/metabolites with ageing in a rat model of Parkinson disease
Authors: Yogesh Singh, Christoph Trautwein, Joan Romani, Madhuri S. Salker, Peter H. Neckel, Isabel Fraccaroli, Mahkameh Abeditashi, Nils Woerner, Jakob Admard, Achal Dhariwal, Morten K. D. Dueholm, Karl-Herbert Schäfer, Florian Lang, Daniel E. Otzen, Hilal A. Lashuel, Olaf Riess, Nicolas Casadei
Journal: Molecular Neurodegeneration (2023)

Abstract Background Braak’s hypothesis states that sporadic Parkinson’s disease (PD) follows a specific progression of pathology from the peripheral to the central nervous system, and this progression can be monitored by detecting the accumulation of alpha-Synuclein (α-Syn) protein. Consequently, there is growing interest in understanding how the gut (commensal) microbiome can regulate α-Syn accumulation, as this could potentially lead to PD. Methods We used 16S rRNA and shotgun sequencing to characterise microbial diversity. 1 H-NMR was employed to understand the metabolite production and intestinal inflammation estimated using ELISA and RNA-sequencing from feces and the intestinal epithelial layer respectively. The Na + channel current and gut permeability were measured using an Ussing chamber. Immunohistochemistry and immunofluorescence imaging were applied to detect the α-Syn protein. LC-MS/MS was used for characterization of proteins from metabolite treated neuronal cells. Finally, Metascape and Ingenuity Pathway Analysis (IPA) bioinformatics tools were used for identification of dysregulated pathways. Results We studied a transgenic (TG) rat model overexpressing the human SNCA gene and found that a progressive gut microbial composition alteration characterized by the reduction of Firmicutes to Bacteroidetes ratio could be detected in the young TG rats. Interestingly, this ratio then increased with ageing. The dynamics of Lactobacillus and Alistipes were monitored and reduced Lactobacillus and increased Alistipes abundance was discerned in ageing TG rats. Additionally, the SNCA gene overexpression resulted in gut α-Syn protein expression and increased with advanced age. Further, older TG animals had increased intestinal inflammation, decreased Na + current and a robust alteration in metabolite production characterized by the increase of succinate levels in feces and serum. Manipulation of the gut bacteria by short-term antibiotic cocktail treatment revealed a complete loss of short-chain fatty acids and a reduction in succinate levels. Although antibiotic cocktail treatment did not change α-Syn expression in the enteric nervous system of the colon, however, reduced α-Syn expression was detected in the olfactory bulbs (forebrain) of the TG rats. Conclusion Our data emphasize that the gut microbiome dysbiosis synchronous with ageing leads to a specific alteration of gut metabolites and can be modulated by antibiotics which may affect PD pathology.
Long-term Outcomes from a Phase 2 Study of Neoadjuvant Chemotherapy for Muscle-invasive Bladder Cancer (SWOG S1314; NCT02177695)
Authors: Thomas W. Flaig, Catherine M. Tangen, Siamak Daneshmand, Ajjai Shivaram Alva, M. Scott Lucia, David James McConkey, Dan Theodorescu, Amir Goldkorn, Matthew I. Milowsky, Rick Bangs, Gary R. MacVicar, Bruno R. Bastos, Jared S. Fowles, Daniel L. Gustafson, Melissa Plets, Ian M. Thompson, Seth P. Lerner
Journal: European Urology (2023)
Passive Alzheimer’s immunotherapy: A promising or uncertain option?
Authors: Poul F. Høilund-Carlsen, Mona-Elisabeth Revheim, Tommaso Costa, Abass Alavi, Kasper P. Kepp, Stefano L. Sensi, George Perry, Nikolaos K. Robakis, Jorge R. Barrio, Bryce Vissel
Journal: Ageing Research Reviews (2023)
Efficacy of immune checkpoint inhibitors for the treatment of advanced melanoma in patients with concomitant chronic lymphocytic leukemia
Authors: S.H. Cass, J.W.D. Tobin, Y.D. Seo, G. Gener-Ricos, E.Z. Keung, E.M. Burton, M.A. Davies, J.L. McQuade, A.J. Lazar, R. Mason, M. Millward, S. Sandhu, C. Khoo, L. Warburton, V. Guerra, A. Haydon, H. Dearden, A.M. Menzies, M.S. Carlino, J.L. Smith, P. Mollee, M. Burgess, S. Mapp, C. Keane, V. Atkinson, S.A. Parikh, S.N. Markovic, W. Ding, T.G. Call, P.J. Hampel, G.V. Long, J.A. Wargo, A. Ferrajoli
Journal: Annals of Oncology (2023)
Abortion Is Essential to Fully Supporting Healthy Surgical Family Building—Reply
Authors: Chantal Reyna, Maria S. Altieri
Journal: JAMA Surgery (2023)

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Authors: Hao Luo, Kenneth Man, Ian Wong
Journal: JAMA Psychiatry (2023)

purpose of our study was to examine within-database differences rather than between-database comparisons.Our study aimed to examine whether rates of antipsychotic drug prescriptions in different countries increased during the COVID-19 pandemic compared with historical rates observed from the same database.By applying common analytics to multiple databases that cover a large population, we conducted a comprehensive assessment across different health care systems and world regions in a single study.Our study generated initial evidence on the potential antipsychotic use reflex in a timely manner to inform health policy and clinical practice. 5The study also provides a basis for further in-depth investigations.